Proteomic analysis of the INS-1E secretome identify novel vitamin D-regulated proteins

Diabetes Metab Res Rev. 2016 Sep;32(6):514-21. doi: 10.1002/dmrr.2777. Epub 2016 Mar 8.

Abstract

Background: Experimental evidence indicates that vitamin D may have a beneficial role in pancreatic β-cell function.

Methods: In the present study, stable isotope labelling by amino acids in cell culture (SILAC) in combination with liquid chromatography-tandem mass spectrometry was used to quantitatively assess the impact of the active vitamin D metabolite, 1,25-(OH)2 D3 , on global protein expression in INS-1E cell secretome.

Results: Twenty-one proteins were found up-regulated (≥1.5 fold changes) and three down-regulated (≤0.67) after treatment of INS-1E cells with 1,25-(OH)2 D3 . Up-regulation of proteins implicated in β-cell growth and proliferation, such as IGF2, IGFBP7 and gelsolin, suggest that 1,25-(OH)2 D3 has a positive effect on β-cell growth and proliferation. Moreover, modulations of several proteins implicated in prohormone processing and insulin exocytosis (IGF2, IGFBP7, Scg5, ProSAAS, Fabp5, Ptprn2 and gelsolin) appear to support the hypothesis that 1,25-(OH)2 D3 plays positive modulatory role in insulin processing and secretion.

Conclusions: Together, we reveal a number of novel vitamin D-regulated proteins that may contribute to a better understanding of the reported beneficial effects of vitamin D on pancreatic β-cells. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: 1,25-dihydroxyvitamin D3; INS-1E; SILAC; proteomics; secretome.

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Calcitriol / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Insulinoma / drug therapy
  • Insulinoma / metabolism*
  • Insulinoma / pathology
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Proteome / analysis*
  • Proteomics / methods
  • Rats
  • Tumor Cells, Cultured

Substances

  • Biomarkers
  • Proteome
  • Calcitriol